Kai M Brown1, Aiqun Xue2, Sohel M Julovi3, Anthony J Gill4, Nick Pavlakis5, Jaswinder S Samra6, Ross C Smith3, Thomas J Hugh2. 1. Cancer Surgery and Metabolism Research Group, University of Sydney, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Northern Clinical School, University of Sydney, Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, New South Wales, Australia. Electronic address: kkai6773@uni.sydney.edu.au. 2. Cancer Surgery and Metabolism Research Group, University of Sydney, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Northern Clinical School, University of Sydney, Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, New South Wales, Australia. 3. Cancer Surgery and Metabolism Research Group, University of Sydney, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia. 4. Cancer Diagnosis and Pathology Group, University of Sydney, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia. 5. Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, New South Wales, Australia. 6. Northern Clinical School, University of Sydney, Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, New South Wales, Australia.
Abstract
BACKGROUND: Few in vivo models for colorectal cancer have been demonstrated to show external validity by accurately predicting clinical patient outcomes. Patient-derived xenograft (PDX) models of cancer have characteristics that might provide a form of translational research leading to personalized cancer care. The aim of this pilot study was to assess the feasibility of using PDXs as a platform for predicting patient colorectal liver metastases responses, in this case by correlating PDX and patient tumor responses to either folinic acid, fluorouracil plus oxaliplatin or folinic acid, fluorouracil plus irinotecan-based regimens. METHODS: Sixteen patients underwent potentially curative resection of colorectal liver metastases, and tumors were grafted into NOD.CB17-Prkdcscid/Arc mice. Mice were divided into groups to determine relative tumor growth in response to treatment. Tumors were analyzed by immunohistochemistry for Ki67 and Excision repair cross-complementation group 1. RESULTS: An engraftment rate of 81% was achieved. Overall, there was a 67% positive match rate between eligible patient and PDX chemosensitivity profiles. There was a significant difference in relative decrease in Ki67 expression between sensitive/stable versus resistant PDXs for both treatment regimens. There was no statistically significant correlation between baseline ERCC1 expression and response to Oxaliplatin + 5-Fluorouracil in the PDXs. CONCLUSIONS: This pilot study supports the feasibility of using PDX models of advanced colorectal cancer in larger studies to potentially predict patient chemosensitivity profiles.
BACKGROUND: Few in vivo models for colorectal cancer have been demonstrated to show external validity by accurately predicting clinical patient outcomes. Patient-derived xenograft (PDX) models of cancer have characteristics that might provide a form of translational research leading to personalized cancer care. The aim of this pilot study was to assess the feasibility of using PDXs as a platform for predicting patientcolorectal liver metastases responses, in this case by correlating PDX and patienttumor responses to either folinic acid, fluorouracil plus oxaliplatin or folinic acid, fluorouracil plus irinotecan-based regimens. METHODS: Sixteen patients underwent potentially curative resection of colorectal liver metastases, and tumors were grafted into NOD.CB17-Prkdcscid/Arc mice. Mice were divided into groups to determine relative tumor growth in response to treatment. Tumors were analyzed by immunohistochemistry for Ki67 and Excision repair cross-complementation group 1. RESULTS: An engraftment rate of 81% was achieved. Overall, there was a 67% positive match rate between eligible patient and PDX chemosensitivity profiles. There was a significant difference in relative decrease in Ki67 expression between sensitive/stable versus resistant PDXs for both treatment regimens. There was no statistically significant correlation between baseline ERCC1 expression and response to Oxaliplatin + 5-Fluorouracil in the PDXs. CONCLUSIONS: This pilot study supports the feasibility of using PDX models of advanced colorectal cancer in larger studies to potentially predict patient chemosensitivity profiles.
Authors: Johannes Klose; Stefan Trefz; Tobias Wagner; Luca Steffen; Arsalie Preißendörfer Charrier; Praveen Radhakrishnan; Claudia Volz; Thomas Schmidt; Alexis Ulrich; Sebastian M Dieter; Claudia Ball; Hanno Glimm; Martin Schneider Journal: PLoS One Date: 2019-02-14 Impact factor: 3.240
Authors: Pedro Cruz-Nova; Michael Schnoor; José Correa-Basurto; Martiniano Bello; Paola Briseño-Diaz; Arturo Rojo-Domínguez; Carlos M Ortiz-Mendoza; Jorge Guerrero-Aguirre; Francisco J García-Vázquez; Rosaura Hernández-Rivas; María Del Rocío Thompson-Bonilla; Miguel Vargas Journal: BMC Cancer Date: 2018-11-01 Impact factor: 4.430